Our present understanding of the immunogenetics of the DL-A histocompatibility complex in the canine species remains insufficient to permit extension of currently available in vitro testing methods to further studies in the mongrel dog population, where applicable data could be of direct interest to clinical problems in bone marrow transplantation. It is the purpose of the proposed continuation studies to pursue additional efforts to define the component(s) of the main histocompatibility complex in the selectively bred lines of animals of known DL-A SD and LD genotypes, in the hope of identifying the other histocompatibility variables capable of conditioning the survival of bone marrow allografts and of other tissues in the canine species. An additional important goal of the studies planned for the coming year is the attempt to extend our current understanding of the cellular and/or humoral mechanisms which permit supralethal total body irradiation and bone marrow transplantation to induce tolerance to tissue allografts in adult dogs in the Cooperstown Colony. The frequency with which fatalities due to graft-versus-host (GVH) disease continues to occur in recipients of genotypically HL-A (human) or DL-A (canine) identical bone marrow allografts remains the focal point of these investigations. Since the one consistent exception to this observation has occurred in the Colony of selectively bred lines of beagles maintained at the Mary Imogene Bassett Hospital in Cooperstown, N.Y., we propose to continue the precise tracing of DL-A genotypes of individual dogs for at least 4 to 5 generations, and to selectively breed on this basis in order to produce additional lines of DL-A identical dogs which, although known to differ by other genetic markers share sufficient non-DL-A histocompatibility determinants to avoid the triggering of GVH reactions after supralethal total body irradiation and bone marrow transplantation. It is hoped that these studies will provide an approach to the eventual application of methods of selection developed in the Cooperstown Colony to more out-bred series of experimental animals, for eventual application to the human situation.